The proposed investigation is a three-year study of the immunology of experimental lymphatic filariasis using the congenitally athymic 'nude' and euthymic 'normal' mouse. Nude C3H/HeN mice which are fully susceptible to infection with Brugia pahangi, and syngeneic normal mice which are immunologically resistant, will be used to study mechanisms of protective immunity especially to the infective third larval stage. Antigens which elicit protective immune response will be isolated and characterized using defined monoclonal antibodies. Humoral and cellular immune responses to larval antigens will be identified in normal mice using standard immunological assays, and further characterized by adoptive transfer of protection to nudes. Reactions to larval antigens in lymphatic tissues of infected mice will be defined by fluorescence microscopy employing monoclonal antibodies to discrete antigens and cell surface markers. Humoral and cellular mechanisms of larval damage will also be observed in vitro, with larval viability assessed by infectivity for nude mice. Somatic, solubilized somatic and exretory-secretory antigens of B. pahangi will be prepared biochemically from materials harvested from intraperiotoneal infections of nude mice. Antigens present in fractions which give positive reactions in immunological assays of cellular and humoral immunity, will be further purified by affinity chromatography on monoclonal antibody-bound columns, followed by biological characterization of protective function in vivo. In further work we hope to continue attempts to establish Wuchereria bancrofti in nude mice. A comparison of the immunobiology and antigenic character of other Brugia species infective for nude mice is also planned. We expect this research to have important applications in the specific immunodiagnosis of human filariasis and in future immunological intervention in the disease process. Prevention of filarial disease by immunization remains a desirable, if long-term goal.